Cell Competition Is Driven by Autophagy

Dev Cell. 2019 Oct 7;51(1):99-112.e4. doi: 10.1016/j.devcel.2019.08.018. Epub 2019 Sep 19.


Cell competition is a quality control process that selectively eliminates unfit cells from the growing tissue via cell-cell interaction. Despite extensive mechanistic studies, the mechanism by which cell elimination is triggered has been elusive. Here, through a genetic screen in Drosophila, we discover that V-ATPase, an essential factor for autophagy, is required for triggering cell competition. Strikingly, autophagy is specifically elevated in prospective "loser" cells nearby wild-type "winner" cells, and blocking autophagy in loser cells abolishes their elimination. Mechanistically, elevated autophagy upregulates a proapoptotic gene hid through NFκB, and the elevated hid cooperates with JNK signaling to effectively induce loser's death. Crucially, this mechanism generally applies to cell competition caused by differences in protein synthesis between cells. Our findings establish a common mechanism of cell competition whereby cells with higher protein synthesis induce autophagy in their neighboring cells, leading to elimination of unfit cells.

Keywords: JNK; NFκB; autophagy; cell competition; cell death; hid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy*
  • Binding, Competitive
  • Cell Communication
  • Cell Death
  • Cell Proliferation
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Female
  • Genotype
  • MAP Kinase Kinase 4 / metabolism*
  • Male
  • Mutation
  • NF-kappa B / metabolism*
  • RNA Interference
  • Signal Transduction
  • Transcriptional Activation
  • Up-Regulation


  • Drosophila Proteins
  • NF-kappa B
  • MAP Kinase Kinase 4